HIT CF and CHOICES; a study investigating a new triple combination CFTR modulator therapy based on organoid responsiveness in people with CF who have rare CFTR mutations

HIT CF and CHOICES: a study using rectal organoids to predict responsiveness of rare CFTR mutations to novel CFTR modulator therapies (HIT CF); followed by a randomised controlled trial to assess clinical responsiveness (CHOICES)

Part 1 of study (now closed):

HIT CF (Human Individualised Therapy in CF).



Part 1 of the study (HIT CF) involved the collection of rectal biopsies from people with CF who have rare CFTR mutations and are not eligible for taking Kaftrio®. These rectal biopsies were used to grow organoids (aka ‘mini-organs’), and a new triple combination CFTR modulator therapy was tested for effectiveness on these organoids in a laboratory before assessing the medication directly in people with CF. This CFTR modulator therapy consists of dirocaftor (CFTR potentiator), posenacaftor (CFTR corrector) and nesolicaftor (CFTR amplifier), developed by FAIR Therapeutics – a Netherlands based biotech company. CFTR modulators help the faulty CFTR protein to function properly.



A proportion of participants who took part in HIT CF and whose organoids showed a good responsiveness to the therapy will be invited to take part in the CHOICES study (Part 2). A proportion of participants who did not respond to the therapy will also be invited to take part in the CHOICES study





Part 2 of the study (CHOICES) will involve assessing the safety and effectiveness of the new triple combination CFTR modulator therapy in participants of the HIT-CF study (Part 1) whose organoids (aka ‘mini-organs’) showed a good response to the treatment. A proportion of non-responders will also be invited to take part for comparison. Participants in CHOICES will receive either the new medication or a placebo and the study will last approximately 42 weeks.